The purpose of this training program is to select talented and committed young investigators and to prepare them for careers in cardiovascular research. This program has been in place at this institution since 1978. A substantial number of our previous trainees remain active in research and have made notable contributions to cardiovascular investigation. We are proud of this tradition, and the current proposal preserves many features of our previously successful program. The only important organizational change since the last competitive renewal in 1997 is the replacement of the Program Director, R. Sanders Williams, M.D., by L. David Hillis, M.D. The 3 Associate Directors (Drs. Eric Olson, Masashi Yanagisawa, and James Stull) remain in place, as do many of the Participating Faculty. We request funds for 8 predoctoral and 16 postdoctoral positions annually (unchanged from previously). Our faculty is multidisciplinary: 55 individuals who represent 10 academic departments and 8 Graduate School programs. The faculty are linked by a common interest in important problems of cardiovascular biology and medicine as well as by an interlocking network of collaborative activities, including several research centers and PPG grants. Cardiovascular research training is offered in 4 general areas: (1) Developmental and Molecular Biology, (2) Vascular Biology, (3) Physiology and Signaling, and (4) Clinical Sciences. This Program gives particular attention to (a) the integration of molecular genetics and biological chemistry with physiological investigations in a broad range of model organisms and human subjects, (b) to issues of scientific integrity and ethics, and (c) to increasing the participation of females and underrepresented minority groups in the training program, both as participants and as faculty.